4.0 Article

Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes

Journal

BEHAVIOURAL PHARMACOLOGY
Volume 18, Issue 5-6, Pages 571-580

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0b013e3282ee2adb

Keywords

cannabinoids; CB1 antagonist; electrophysiology; endocannabinoids; hippocampus; memory

Funding

  1. NCI NIH HHS [CA08549] Funding Source: Medline
  2. NIDA NIH HHS [DA03502, DA07625, DA00119] Funding Source: Medline
  3. NIMH NIH HHS [MH613972] Funding Source: Medline

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Population codes derived from ensembles of hippocampal neurons were assessed to determine whether endocannabinoids were active when rats performed a delayed-non match-to-sample (DNMS) short-term memory task. Multivariate discriminant analyses of the firing patterns of ensembles of CA1 and CA3 hippocampal neurons extracted representations of information encoded at the time of the sample response (SmR codes) during individual DNMS trials. The 'strength' or distinctiveness of trial-specific SmR codes in normal sessions was compared with sessions in which either rimonabant, the well-characterized cannabinoid CB1 receptor antagonist, or WIN 55212-2 (WIN-2), a cannabinoid CB1 receptor agonist, were administered. Results show that performance on trials with delay intervals longer than 10 s was facilitated by rimonabant (2.0 mg/kg) owing to a significantly increased frequency of trials with stronger SmR codes. In contrast, WIN-2 (0.35 mg/kg) suppressed the strength of SmR codes necessary to perform trials with delays greater than 10 s. The positive influence of rimonabant on performance indicated that the action of endocannabinoids was to reduce SmR code strength, resulting in trials that were at risk for errors if the delay exceeded 10 s. Thus endocannabinoids, like exogenously administered cannabinoids, reduced hippocampal encoding necessary to perform long-delay trials. The findings therefore indicate a direct relationship between the actions of endocannabinoids on hippocampal processes and the ability to encode information into short-term memory.

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